One-Step Colloidal Synthesis of Non-Toxic Electroactive Carbon Dots with a Better Threshold Cytotoxicity and Cytocompatibility

Abstract

Carbon dots (CDs), because of their characteristic size (<10 nm) and highly fluorescent nature, can be internalized in biological cells or can be tagged to the key components of a living system. While these attributes can be potentially exploited for biomedical applications, the toxicity of CDs remains an important issue to be addressed. Both the synthesis approach and morphological attributes critically determine the dose-dependent toxicity and cytocompatibility of CDs. Against this perspective, we report herein a one-step colloidal synthesis of CDs using different reaction solvents that lead to the formation of three types of CDs (type I, type II, and type III CDs). The cytocompatibility and cellular uptake of CDs in human mesenchymal stem cells (hMSCs) are dependent on the nature of functionalization and concomitantly on the type of precursors. In particular, type I CDs are synthesized using citric acid, hexadecylamine, and octadecene that are immiscible in culture media. The type II CDs synthesized using citric acid and octadecene emit green fluorescence at a 488 nm excitation and were found to be agglomerated when internalized in hMSCs, whereas the type III CDs, synthesized using citric acid and deionized water, exhibit an agglomeration-free behavior. Further, type III CDs show a wide particle distribution, wide emission bandwidth range of 280–700 nm, threshold toxicity of 1 mg/mL, and good cytocompatibility with hMSCs, much better than those in the published reports. When benchmarked against commercial graphene quantum dots, the as-synthesized type III CDs have better electrical conductivity and cytocompatibility at a given dosage. Thus, the electroactive nature of synthesized type III CDs along with their inherent fluorescent property and less cytotoxicity would enable their potential applications in bio-imaging, directional lineage commitment, and cell-based therapy.

Fluorescent Nanocarbons: From Synthesis and Structure to Cancer Imaging and Therapy

“…[398] In addition, the cytotoxicity of CDs with different surface modifications has been extensively studied against both animal and human cells. [399][400][401][402] A majority of these studies have suggested that CDs, regardless of surface passivation, do not indicate evidence of toxicity [403] or have identified negligible toxicity [404] when there is great cellular uptake ability that enables easy penetration into cells. An investigation into cellular morphological changes also revealed that CDs conjugated with polymers carrying neutral surface charge do not induce any defined abnormalities in cellular structure and functions when they are used under low concentrations.…”

Green synthesis of carbon dots from fish scales for selective turn off–on detection of glutathione

“…Carbon dots (CDs) are a type of novel carbon nanoparticle with sp 2 hybridized carbon nanostructures and an average particle size less than 10 nm. 15 CDs have superior luminescence and biocompatibility, making them attractive for biomarkers, nanoscale uorescent probes, and biological imaging applications. [16][17][18] Because CDs contain many carboxylic acid moieties at their surface and can possess variable surface functionalities, microstructures, surface state, and crystalline state, they have a wide range of applications in addition to their use in sensing, drug delivery, environmental pollutant monitoring, diagnosis, and treatment of diseases.…”

EGTA-Derived Carbon Dots with Bone-Targeting Ability: Target-Oriented Synthesis and Calcium Affinity

“…The synthesis of CDs has remained a challenge, with low synthetic yields being a major issue. CDs possess unique properties such as fluorescence, good biocompatibility, and low toxicity, − making them useful in many fields such as sensing, − imaging, − catalysis, , drug delivery, − and device − applications. CDs have excellent fluorescence ability, and solid-state silane-functionalized CDs can be directly used as phosphors for multicolor light-emitting diodes and all types of white light-emitting diodes .…”